High- vs Standard-Dose Intravenous Magnesium for Acute Headache
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Monastir
About this trial
Headache is one of the most common reasons for consultation in emergency departments and represents a significant cause of disability, particularly in patients with migraine and other primary headache disorders. Despite the availability of several analgesic treatments, including nonsteroidal anti-inflammatory drugs and paracetamol, pain relief is often incomplete, and a proportion of patients require additional rescue therapy.
Magnesium sulfate has emerged as a potential therapeutic option in acute headache due to its role in modulating neuronal excitability, vascular tone, and pain-related neurotransmitter release. However, its efficacy as a standalone treatment, the optimal intravenous dose, and its comparative effectiveness versus standard therapy remain unclear.
This randomized, double-blind, controlled trial aims to evaluate the efficacy and safety of intravenous magnesium sulfate in the treatment of acute non-traumatic headache in the emergency department. Participants will be randomly assigned to receive either low-dose magnesium sulfate (2 g IV), high-dose magnesium sulfate (4 g IV), or intravenous paracetamol (1 g IV) as an active comparator.
The primary outcome is the change in pain intensity measured using the Visual Analog Scale (VAS) at 60 minutes after treatment administration, as well as the proportion of patients achieving at least 50% pain reduction. Secondary outcomes include time course of pain relief, need for rescue medication, adverse events, patient satisfaction, and length of stay in the emergency department.
In addition, the study will assess baseline ionized magnesium levels to explore their relationship with treatment response and evaluate whether magnesium levels may predict clinical efficacy.
The results of this study may help clarify the role of intravenous magnesium sulfate in the management of acute headache and potentially improve treatment strategies in emergency settings.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥18 years
Presentation to the emergency department with acute non-traumatic headache of less than 72 hours duration
Migraine
Tension-type headache
Disqualifiers
Suspected or confirmed secondary headache (e.g., intracranial hemorrhage, infection, mass lesion)
Recent head trauma
Known hypersensitivity or contraindication to magnesium sulfate or paracetamol
Use of analgesic medication within the previous 6 hours
Trial design
Design model
Parallel
Treatments tested in this trial
Magnesium Sulfate 2 grams
DrugParticipants assigned to this arm will receive intravenous magnesium sulfate 2 g diluted in 100 mL of 0.9% sodium chloride administered over 10-15 minutes, along with a matching placebo for paracetamol. Infusions will be prepared in identical formats to maintain blinding. Continuous monitoring of vital signs will be performed during and after administration. Rescue medication may be administered from 30 minutes if predefined criteria are met.
Magnesium Sulfate 4 G
DrugParticipants assigned to this arm will receive intravenous magnesium sulfate 4 g diluted in 100 mL of 0.9% sodium chloride administered over 10-15 minutes, along with a matching placebo for paracetamol.. Infusions will be prepared in identical formats to maintain blinding. Continuous monitoring of vital signs will be performed during and after administration. Rescue medication may be administered from 30 minutes if predefined criteria are met.
Paracetamol 1 g
DrugParticipants assigned to this arm will receive intravenous paracetamol 1 g administered over 10-15 minutes, along with a matching placebo for magnesium (100 mL of 0.9% sodium chloride). Infusions will be prepared in identical formats to maintain blinding. Continuous monitoring of vital signs will be performed during and after administration. Rescue medication may be administered from 30 minutes if predefined criteria are met.
Treatment groups
300 Participants
are divided into 3 treatment groupsGroup A: Magnesium Sulfate 2 g IVActive comparator 1 intervention
Group B: Magnesium Sulfate 4 g IVActive comparator 1 intervention
Group C: Paracetamol 1 g IVActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
Change in Pain Intensity at 60 Minutes
Change in pain intensity measured using the Visual Analog Scale (VAS, 0-10) from baseline to 60 minutes after treatment administration
Time frame
60 minutes2
Proportion of Responders at 60 Minutes
Proportion of participants achieving a ≥50% reduction in VAS pain score from baseline at 60 minutes.
Time frame
60 minutesSecondary outcomes
1
Pain Intensity Over Time
Area under the curve (AUC) of VAS pain scores measured from baseline to 120 minutes.
Time frame
0 to 120 minutes2
Time to Clinically Meaningful Pain Relief
Time from treatment administration to achievement of clinically meaningful pain relief, defined as VAS ≤3 or ≥50% reduction from baseline.
Time frame
Up to 120 minutes3
Use of Rescue Medication
Proportion of participants requiring rescue analgesia after 30 minutes due to insufficient pain relief.
Time frame
30 to 120 minutes4
Adverse Events
Incidence and type of treatment-emergent adverse events during the observation period.
Time frame
0 to 120 minutesOther outcomes
1
Patient Satisfaction
Patient-reported satisfaction with treatment using a standardized scale.
Time frame
120 minutes2
Association Between Ionized Magnesium and Treatment Response
Relationship between baseline ionized magnesium levels and analgesic response at 60 minutes.
Time frame
Baseline to 60 minutesSponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov